1887

Abstract

Trigeminal ganglion (TG) neurons are important target cells for many alphaherpesviruses, constituting major sites for latency/reactivation events. Here, the kinetics of productive infection of the swine alphaherpesvirus pseudorabies virus (PRV) and resulting cell death in primary porcine TG neurons were determined, and these were compared with similar kinetics in many other porcine cell types. Confocal microscopy showed that all TG neurons expressed late genes such as viral glycoproteins, and that these glycoproteins were processed through the Golgi and reached the cell surface as in other cell types, albeit with a delay of ±2–6 h. However, TG neurons were much more resistant towards PRV-induced cell death compared with all other porcine cell types tested (non-neuronal TG cells, superior cervical ganglion neurons, epithelial kidney cells, arterial endothelial cells, dermal fibroblasts and cells derived from a porcine swine kidney cell line). About half of the TG neurons survived up to 96 h post-inoculation (end of experiment), whereas all other cell types almost completely succumbed within 2 days post-inoculation. In addition, infection with a strongly pro-apoptotic PRV strain that misses the anti-apoptotic US3 protein did not lead to substantial apoptosis in TG neurons, even at 72 h post-inoculation. Thus, primary porcine TG neurons can be infected with PRV , and are remarkably more resistant to PRV-induced cell death compared with other porcine cell types, suggesting a cell type-specific resistance to alphaherpesvirus-induced cell death that may have important implications for different aspects of the virus life cycle, including latency/reactivation events.

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2005-05-01
2019-10-18
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References

  1. Aleman, N., Quiroga, M. I., López-Pena, M., Vásquez, S., Guerrero, F. H. & Nieto, J. M. ( 2001; ). Induction and inhibition of apoptosis by pseudorabies virus in the trigeminal ganglion during acute infection of swine. J Virol 75, 469–479.[CrossRef]
    [Google Scholar]
  2. Aubert, M. & Blaho, J. A. ( 2001; ). Modulation of apoptosis during herpes simplex virus infection in human cells. Microbes Infect 3, 859–866.[CrossRef]
    [Google Scholar]
  3. Baskerville, A., McFerran, J. B. & Dow, C. ( 1973; ). Aujeszky's disease in pigs. Vet Bull 43, 465–480.
    [Google Scholar]
  4. Bearer, E. L., Breakefield, X. O., Schuback, D., Reese, T. S. & LaVail, J. H. ( 2000; ). Retrograde axonal transport of herpes simplex virus: evidence for a single mechanism and a role for tegument. Proc Natl Acad Sci U S A 97, 8146–8150.[CrossRef]
    [Google Scholar]
  5. Cantin, E. M., Hinton, D. R., Chen, J. & Openshaw, H. ( 1995; ). Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1. J Virol 69, 4898–4905.
    [Google Scholar]
  6. Ensor, E., Smith, M. D. & Latchman, D. S. ( 2001; ). The BRN-3A transcription factor protects sensory but not sympathetic neurons from programmed cell death/apoptosis. J Biol Chem 276, 5204–5212.[CrossRef]
    [Google Scholar]
  7. Favoreel, H. W., Mettenleiter, T. C. & Nauwynck, H. J. ( 2004; ). Copatching and lipid raft association of different viral glycoproteins expressed on the surfaces of pseudorabies virus-infected cells. J Virol 78, 5279–5287.[CrossRef]
    [Google Scholar]
  8. Geenen, K., Favoreel, H. W., Olsen, L., Enquist, L. W. & Nauwynck, H. J. ( 2005; ). The pseudorabies virus US3 protein kinase possesses anti-apoptotic activity that protects cells from apoptosis during infection and after treatment with sorbitol or staurosporine. Virology 331, 144–150.[CrossRef]
    [Google Scholar]
  9. Geiger, K. D., Gurushanthaiah, D., Howes, E. L., Lewandowski, G. A., Reed, J. C., Bloom, F. E. & Sarvetnick, N. E. ( 1995; ). Cytokine-mediated survival from lethal herpes simplex virus infection: role of programmed neuronal death. Proc Natl Acad Sci U S A 92, 3411–3415.[CrossRef]
    [Google Scholar]
  10. Geiger, K. D., Nash, T. C., Sawyer, S. & 7 other authors ( 1997; ). Interferon-γ protects against herpes simplex virus type 1-mediated neuronal death. Virology 238, 189–197.[CrossRef]
    [Google Scholar]
  11. Hood, C., Cunningham, A. L., Slobedman, B., Boadle, R. A. & Abendroth, A. ( 2003; ). Varicella-zoster virus-infected human sensory neurons are resistant to apoptosis, yet human foreskin fibroblasts are susceptible: evidence for a cell-type-specific apoptotic response. J Virol 77, 12852–12864.[CrossRef]
    [Google Scholar]
  12. Khanna, K. M., Bonneau, R. H., Kinchington, P. R. & Hendricks, R. L. ( 2003; ). Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity 18, 593–603.[CrossRef]
    [Google Scholar]
  13. Linford, N. J., Yang, Y., Cook, D. G. & Dorsa, D. M. ( 2001; ). Neuronal apoptosis resulting from high doses of the isoflavone genistein: role for calcium and p42/44 mitogen-activated protein kinase. J Pharmacol Exp Ther 299, 67–75.
    [Google Scholar]
  14. Linstedt, A. D. & Hauri, H.-P. ( 1993; ). Giantin, a novel conserved Golgi membrane protein containing a cytoplasmic domain of at least 350 kDa. Mol Biol Cell 4, 679–693.[CrossRef]
    [Google Scholar]
  15. Liu, T., Khanna, K. M., Carriere, B. N. & Hendricks, R. L. ( 2001; ). Gamma interferon can prevent herpes simplex virus type 1 reactivation from latency in sensory neurons. J Virol 75, 11178–11184.[CrossRef]
    [Google Scholar]
  16. Lovato, L., Inman, M., Henderson, G., Doster, A. & Jones, C. ( 2003; ). Infection of cattle with bovine herpes virus 1 strain that contains a mutation in the latency-related gene leads to increased apoptosis in trigeminal ganglia during the transition from acute infection to latency. J Virol 77, 4848–4857.[CrossRef]
    [Google Scholar]
  17. Ma, L., Lei, L., Eng, S. R., Turner, E. & Parada, L. F. ( 2003; ). Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons. Development 130, 3525–3534.[CrossRef]
    [Google Scholar]
  18. Nauwynck, H. J. & Pensaert, M. B. ( 1992; ). Abortion induced by cell-associated pseudorabies virus in vaccinated sows. Am J Vet Res 53, 489–493.
    [Google Scholar]
  19. Nauwynck, H. J. & Pensaert, M. B. ( 1995; ). Effect of specific antibodies on the cell-associated spread of pseudorabies virus in monolayers of different cell types. Arch Virol 140, 1137–1146.[CrossRef]
    [Google Scholar]
  20. Oakes, J. E. & Lausch, R. N. ( 1984; ). Monoclonal antibodies suppress replication of herpes simplex virus type 1 in trigeminal ganglia. J Virol 51, 656–661.
    [Google Scholar]
  21. Perng, G.-C., Jones, C., Ciacci-Zanelle, J. & 8 other authors ( 2000; ). Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287, 1500–1503.[CrossRef]
    [Google Scholar]
  22. Preston, C. M. ( 2000; ). Repression of viral transcription during herpes simplex virus latency. J Gen Virol 81, 1–19.
    [Google Scholar]
  23. Rajcani, J. & Durmanova, V. ( 2000; ). Early expression of herpes simplex virus (HSV) proteins and reactivation of latent infection. Folia Microbiol 45, 7–28.[CrossRef]
    [Google Scholar]
  24. Riedy, M. C., Muirhead, K. A., Jensen, C. P. & Stewart, C. C. ( 1991; ). Use of a photolabeling technique to identify nonviable cells in fixed homologous or heterologous cell populations. Cytometry 12, 133–139.[CrossRef]
    [Google Scholar]
  25. Sainz, B., Jr & Halford, W. P. ( 2002; ). Alpha/beta interferon and gamma interferon synergize to inhibit the replication of herpes simplex virus type 1. J Virol 76, 11541–11550.[CrossRef]
    [Google Scholar]
  26. Sawtell, N. M. ( 1997; ). Comprehensive quantification of herpes simplex virus latency at single-cell level. J Virol 71, 5423–5431.
    [Google Scholar]
  27. Schijns, V. E., Van der Neut, R., Haagmans, B. L., Bar, D. R., Schellekens, H. & Horzinek, M. C. ( 1991; ). Tumour necrosis factor-α, interferon-γ and interferon-β exert antiviral activity in nervous tissue cells. J Gen Virol 72, 809–815.[CrossRef]
    [Google Scholar]
  28. Shimeld, C., Whiteland, J. L., Williams, N. A., Easty, D. L. & Hill, T. J. ( 1997; ). Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1. J Gen Virol 78, 3317–3325.
    [Google Scholar]
  29. Simmons, A. & Tscharke, D. C. ( 1992; ). Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. J Exp Med 175, 1337–1344.[CrossRef]
    [Google Scholar]
  30. Smith, M. D., Dawson, S. J., Boxer, L. M. & Latchman, D. S. ( 1998a; ). The N-terminal domain unique to the long form of the Brn-3a transcription factor is essential to protect neuronal cells from apoptosis and for the activation of Bcl-2 gene expression. Nucleic Acids Res 26, 4100–4107.[CrossRef]
    [Google Scholar]
  31. Smith, M. D., Ensor, E. A., Coffin, R. S., Boxer, L. M. & Latchman, D. S. ( 1998b; ). Bcl-2 transcription from the proximal P2 promoter is activated in neuronal cells by the Brn-3a POU family transcription factor. J Biol Chem 273, 16715–16722.[CrossRef]
    [Google Scholar]
  32. Smith, M. D., Melton, L. A., Ensor, E. A., Packham, G., Anderson, P., Kinloch, R. A. & Latchman, D. S. ( 2001; ). Brn-3a activates the expression of Bcl-xL and promotes neuronal survival in vivo as well as in vitro. Mol Cell Neurosci 17, 460–470.[CrossRef]
    [Google Scholar]
  33. Smith, G. A., Pomeranz, L., Gross, S. P. & Enquist, L. W. ( 2004; ). Local modulation of plus-end transport targets herpesvirus entry and egress in sensory axons. Proc Natl Acad Sci U S A 101, 16034–16039.[CrossRef]
    [Google Scholar]
  34. Tomishima, M. J., Smith, G. A. & Enquist, L. W. ( 2001; ). Sorting and transport of alpha herpesviruses in axons. Traffic 2, 429–436.[CrossRef]
    [Google Scholar]
  35. Van de Walle, G. R., Favoreel, H. W., Nauwynck, H. J., Mettenleiter, T. C. & Pensaert, M. B. ( 2003; ). Transmission of pseudorabies virus from immune-masked blood monocytes to endothelial cells. J Gen Virol 84, 629–637.[CrossRef]
    [Google Scholar]
  36. van Zijl, M., van der Gulden, H., de Wind, N., Gielkens, A. & Berns, T. G. ( 1990; ). Identification of two genes in the unique short region of pseudorabies virus: comparison with herpes simplex virus and varicella-zoster virus. J Gen Virol 71, 1747–1755.[CrossRef]
    [Google Scholar]
  37. Wang, J. M., Partoens, P. M., Callebaut, D. P., Coen, E. P., Martin, J.-J. & De Potter, W. P. ( 1995; ). Phenotype plasticity and immunocytochemical evidence for ChAT and DβH co-localization in fetal pig superior cervical ganglion cells. Brain Res Dev Brain Res 90, 17–23.[CrossRef]
    [Google Scholar]
  38. Yang, L., Voytek, C. C. & Margolis, T. P. ( 2000; ). Immunohistochemical analysis of primary sensory neurons latently infected with herpes simplex virus type 1. J Virol 74, 209–217.[CrossRef]
    [Google Scholar]
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